Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000778807 | SCV000915187 | uncertain significance | COG5-congenital disorder of glycosylation | 2018-11-19 | criteria provided, single submitter | clinical testing | This variant results in a frameshift and is predicted to result in premature termination of the protein. It was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018) and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score for this variant, it could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene and cDNA change, and amino acid change. No publications were found based on this search. Due to the potential impact of frameshift variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for this disease. |
| Labcorp Genetics |
RCV000778807 | SCV003459109 | pathogenic | COG5-congenital disorder of glycosylation | 2023-12-08 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ala235Valfs*6) in the COG5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COG5 are known to be pathogenic (PMID: 23228021). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has not been reported in the literature in individuals affected with COG5-related conditions. For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV004027310 | SCV004928012 | pathogenic | Inborn genetic diseases | 2023-12-20 | criteria provided, single submitter | clinical testing | The c.704_706delCCCinsTAGTGGAATT (p.A235Vfs*6) alteration, located in exon 7 (coding exon 7) of the COG5 gene, consists of an deletion of 3 and insertion of 10 nucleotides causing a translational frameshift at position 704 with a predicted alternate stop codon after 6 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, the TAGTGGAATT allele has an overall frequency of 0.001% (2/250944) total alleles studied. The highest observed frequency was 0.003% (1/34576) of Latino alleles. This alteration was detected in conjunction with another alteration in COG5 in one individual with clinical features consistent with COG5-congenital disorder of glycosylation (Mostile, 2019). Based on the available evidence, this alteration is classified as pathogenic. |